A5057160197- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Cardiomyopathy and Myosin Studies
- Atrial Fibrillation Management and Outcomes
- Cardiac Imaging and Diagnostics
- Cardiovascular Function and Risk Factors
- Receptor Mechanisms and Signaling
- Cardiac Ischemia and Reperfusion
- Cardiac Fibrosis and Remodeling
- Neuroscience and Neural Engineering
- Cardiac pacing and defibrillation studies
- Endoplasmic Reticulum Stress and Disease
- Signaling Pathways in Disease
- Cellular Mechanics and Interactions
- Tissue Engineering and Regenerative Medicine
- Adipose Tissue and Metabolism
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Muscle Physiology and Disorders
- Adenosine and Purinergic Signaling
- Heart Rate Variability and Autonomic Control
- Ion Channels and Receptors
- COVID-19 Clinical Research Studies
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Alcohol Consumption and Health Effects
University Hospital Regensburg
2015-2024
Heidelberg University
2009-2017
University Hospital Heidelberg
2013-2017
German Centre for Cardiovascular Research
2013-2017
Universitätsmedizin Göttingen
2017
University of California, San Diego
2009-2017
TU Dresden
2017
West German Heart and Vascular Center Essen
2016
University of Szeged
2016
University Medical Center Hamburg-Eppendorf
2014-2016
Background— The recent breakthrough in the generation of induced pluripotent stem (iPS) cells, which are almost indistinguishable from embryonic (ES) facilitates murine disease– and human patient–specific cell lines. aim this study was to characterize cardiac differentiation potential a iPS clone comparison well-established ES line. Methods Results— With use standard embryoid body–based protocol for cells as well were differentiated 24 days. Although analyzed showed delayed less efficient...
Acute and chronic injuries to the heart result in perturbation of intracellular calcium signaling, which leads pathological cardiac hypertrophy remodeling. Calcium/calmodulin-dependent protein kinase II (CaMKII) has been implicated transduction signals heart, but specific isoforms CaMKII that mediate signaling have not fully defined. To investigate potential involvement disease CaMKIIdelta, major isoform expressed we generated CaMKIIdelta-null mice. These mice are viable display no overt...
Although research suggests that diastolic Ca(2+) levels might be increased in atrial fibrillation (AF), this hypothesis has never been tested. Diastolic leak from the sarcoplasmic reticulum (SR) increase and play a role triggering or maintaining AF by transient inward currents through Na(+)/Ca(2+) exchange. In ventricular myocardium, ryanodine receptor type 2 (RyR2) phosphorylation Ca(2+)/calmodulin-dependent protein kinase (CaMK)II is emerging as an important mechanism for SR leak.We tested...
Background— Atrial fibrillation (AF) is a growing public health problem without adequate therapies. Angiotensin II and reactive oxygen species are validated risk factors for AF in patients, but the molecular pathways connecting unknown. The Ca 2+ /calmodulin-dependent protein kinase (CaMKII) has recently emerged as species–activated proarrhythmic signal, so we hypothesized that oxidized CaMKIIδ could contribute to AF. Methods Results— We found CaMKII was increased atria from patients...
Rationale: Heart failure (HF) is known to be associated with increased Ca 2+ /calmodulin-dependent protein kinase (CaMK)II expression and activity. There still controversial discussion about the functional role of CaMKII in HF. Moreover, inhibition has never been investigated human myocardium. Objective: We sought investigate detailed CaMKIIδ end-stage failing hearts (dilated ischemic cardiomyopathy) effects on contractility. Methods Results: Expression analysis revealed that CaMKIIδ, both...
Background— Transgenic (TG) Ca/calmodulin-dependent protein kinase II (CaMKII)δ C mice have heart failure and isoproterenol (ISO)-inducible arrhythmias. We hypothesized that CaMKII contributes to arrhythmias underlying cellular events inhibition of reduces cardiac arrhythmogenesis in vitro vivo. Methods Results— Under baseline conditions, isolated myocytes from TG showed an increased incidence early afterdepolarizations compared with wild-type ( P <0.05). (AIP) completely abolished these...
Myocardial diastolic stiffness and cardiomyocyte passive force (F(passive)) depend in part on titin isoform composition phosphorylation. Ca(2+)/calmodulin-dependent protein kinase-II (CaMKII) phosphorylates ion channels, Ca(2+)-handling proteins, chromatin-modifying enzymes the heart, but has not been known to target titin.To elucidate whether CaMKII modulates F(passive) normal failing myocardium.Titin phosphorylation was assessed CaMKIIδ/γ double-knockout (DKO) mouse, transgenic...
Sarcoplasmic reticulum (SR) Ca(2+) leak through ryanodine receptor type 2 (RyR2) dysfunction is of major pathophysiological relevance in human heart failure (HF); however, mechanisms underlying progressive RyR2 dysregulation from cardiac hypertrophy to HF are still controversial.We investigated healthy control myocardium (n=5) and patients with compensated (n=25) (n=32). In hypertrophy, Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) A (PKA) both phosphorylated at levels that were not...
Phosphatase inhibitor-1 (I-1) is a distal amplifier element of β-adrenergic signaling that functions by preventing dephosphorylation downstream targets. I-1 downregulated in human failing hearts, while overexpression constitutively active mutant form (I-1c) reverses contractile dysfunction mouse suggesting I-1c may be candidate for gene therapy. We generated mice with conditional cardiomyocyte-restricted expression (referred to herein as dTGI-1c mice) on an I-1–deficient background. Young...
Telethonin (also known as titin-cap or t-cap) is a 19-kDa Z-disk protein with unique β-sheet structure, hypothesized to assemble in palindromic way the N-terminal portion of titin and constitute signalosome participating process cardiomechanosensing. In addition, variety telethonin mutations are associated development several different diseases; however, little about underlying molecular mechanisms telethonin's vivo function.Here we aim investigate role identify disease result its...
Highlights•AS105 is a novel, pyrimidine-based ATP-competitive CaMKII-inhibitor.•It in this manner also effective against autophosphorylated CaMKII (as opposed to KN-93).•AS105 does not negatively affect basal excitation-contraction-coupling cardiomyocytes.•In cardiomyocytes from CaMKIIδC-overexpressing mice with heart failure, AS105 reduces SR Ca2+-leak, thus improving Ca2+-accumulation, leading improved systolic function.•AS105 Ca2+-leak human atrial cardiomyocytes, suppressing...
Abstract Aims Melusin is a muscle-specific chaperone protein whose expression required for compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in setting myocardial infarction (MI) using comprehensive multicentre approach. Methods and results Mice overexpressing heart (TG) wild-type controls (WT) were subjected permanent LAD ligation both acute (Day 3) subsequent remodelling (2 weeks) examined. Mortality mice was significant...
The mitogen-activated protein kinase (MAPK)-activated kinases 2 and 3 (MK2/3) represent downstream of the p38 MAPK. Using MK2/3 double-knockout (MK2/3(-/-)) mice, we analyzed role in cross-striated muscle by transcriptome proteome analyses histology. We demonstrated enhanced expression slow oxidative skeletal myofiber gene program, including peroxisome proliferator-activated receptor gamma (PPARγ) coactivator 1α (PGC-1α). reporter electrophoretic gel mobility shift assays, that MK2 catalytic...
Leaky ryanodine receptor does not contribute to heart failure progression, but its normalization reduces arrhythmias and thereby improves survival in mice.
Background— Considerable evidence suggests that calcium/calmodulin-dependent protein kinase II (CaMKII) overactivity plays a crucial role in the pathophysiology of heart failure (HF), condition characterized by excessive β-adrenoceptor (β-AR) stimulation. Recent studies indicate significant cross talk between β-AR signaling and CaMKII activation presenting as possible downstream mediator detrimental HF. In this study, we investigated effect chronic blocker treatment on activity human...
Abstract Aims Hyperactivity of Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII) has emerged as a central cause pathologic remodelling in heart failure. It been suggested that CaMKII‐induced hyperphosphorylation the ryanodine receptor 2 (RyR2) and consequently increased diastolic leak from sarcoplasmic reticulum (SR) is crucial mechanism by which CaMKII activity leads to contractile dysfunction. We aim evaluate relevance CaMKII‐dependent RyR2 phosphorylation for failure development vivo...
Background: Chronic heart failure (HF) is associated with altered signal transduction via β-adrenoceptors and G proteins reduced cAMP formation. Nucleoside diphosphate kinases (NDPKs) are enriched at the plasma membrane of patients end-stage HF, but functional consequences this largely unknown, particularly for NDPK-C. Here, we investigated potential role NDPK-C in cardiac formation contractility. Methods: Real-time polymerase chain reaction, (far) Western blot, immunoprecipitation,...
AimsEthanol has acute negative inotropic and arrhythmogenic effects. The underlying mechanisms, however, are largely unknown. Sarcoplasmic reticulum Ca2+-leak is an important mechanism for reduced contractility arrhythmias. can be induced by oxidative stress Ca2+/Calmodulin-dependent protein kinase II (CaMKII). Therefore, we investigated the influence of ethanol exposure on excitation-contraction coupling in atrial ventricular cardiomyocytes.Methods resultsIsolated human murine or...